Dexamethasone and cardiac potassium currents in the diabetic rat.
Experiments were designed to compare effects of dexamethasone on transient (Ipeak) and sustained (Isus) K+ currents in control and diabetic rat myocytes. Ventricular myocytes were isolated from control or type 1 streptozotocin (STZ)-induced diabetic male and female rats. Currents were measured using whole-cell voltage-clamp methods. Incubation of cells from control males or females with 100 nM dexamethasone (5-9 h) significantly (P<0.005) augmented Isus (by 28-31%). Ipeak was unchanged. Isus augmentation was abolished by cycloheximide or cytochalasin D, but not by inhibition of protein kinases A or C. Inhibition of tyrosine kinases by genistein (but not its inactive analog genistin) prevented the increase of Isus by dexamethasone. In marked contrast, dexamethasone had a significantly (P<0.015) smaller effect on Isus (11% increase) in cells from male STZ-diabetic rats, as compared to control cells. However, Isus augmentation in cells from female STZ-diabetic rats was normal (31% increase). In ovariectomized-diabetic rats, Isus was unchanged by dexamethasone. The reduced effect in diabetic males might be due to preactivation of tyrosine kinases linking dexamethasone to current modulation. In conclusion, type I diabetes is associated with gender-specific changes in sensitivity of K+ currents to glucocorticoids, linked to alterations in tyrosine-phosphorylated proteins.[1]References
- Dexamethasone and cardiac potassium currents in the diabetic rat. Shimoni, Y. Br. J. Pharmacol. (2005) [Pubmed]
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